ASCO GU: TiNivo-2: Comparing Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor

( In a poster presentation on the third day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022 on Renal Cell Cancer; Adrenal, Penile, Urethral, and Testicular Cancers, Dr. Choueiri presented the rationale and design of the TiNivo-2 trial, examining tivozanib with or without nivolumab in patients with renal cell carcinoma (RCC) who have progressed following one or two lines of therapy, one of which was an immune checkpoint inhibitor.

Tivozanib is a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor which has demonstrated single-agent efficacy in advanced renal cell carcinoma (aRCC). Further, compared with other tyrosine kinase inhibitors, it exhibits minimal off-target toxicities and a favorable adverse event (AE) profile. Prior work led to the FDA approval of tivozanib monotherapy for patients with aRCC who had progressed on 2 or more prior lines of therapy. In the phase 1/2 TiNivo trial, the combination of tivozanib and nivolumab (NCT03136627) demonstrated promising oncologic outcomes and a favorable safety profile.

Thus, the TiNivo-2 trial (NCT04987203) seeks to compare this combination to tivozanib monotherapy in a phase 3, randomized, controlled, multicenter, open-label study. Eligible patients will be adults (age >18 years) with clear cell RCC, ECOG PS 0-1, and disease progression during or following at least 6 weeks of treatment with ICI for RCC, whether in the first or second line setting. Subjects will be stratified by IMDC risk category and whether ICI was received in most recent line of treatment or not.

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In both arms, subjects will receive Tivozanib once daily for 21 consecutive days followed by 7 days off. In the combination arm, subjects will also receive Nivolumab 480mg intravenously every 4 weeks.

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Study assessments include CT scan or MRI of the chest, abdomen, and pelvis every 8 weeks following Cycle 1 Day 1 for 2 years and every 12 weeks thereafter until disease progression is confirmed by independent radiology review.

The primary study endpoint is progression-free survival (PFS) by blinded independent radiological review. A sample size of 326 subjects, with 191 events will provide at least 80% power to detect a 50% improvement in PFS from 8 to 12 months, as assessed by an IRR. Secondary endpoints include assessment of overall survival (OS), objective response rate (ORR), and duration of response (DoR), as well as safety and tolerability. Exploratory endpoints are to assess the quality of life (FKSI-DRS and EORTC QLQ C-30) and to investigate the pharmacokinetics of tivozanib.

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The TiNivo-2 trial is actively enrolling and planning to open at approximately 200 sites in the North and South America, the European Union, and Australia.

Presented by: Toni K. Choueiri MD, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022